A steep decline in diastolic blood pressure over early to mid-life is associated with tau-PET burden in dementia-free adults

Background The relationship between blood pressure (BP) trajectories across early (∼40 years) into mid-life (∼55 years) and preclinical dementia has not previously been well studied using positron emission tomography (PET) imaging outcomes. Objective To examine the association between BP trajectories across early mid-life into mid mid-life and amyloid- and tau-PET burden in adults without clinical dementia. Methods This prospective cohort study included dementia-free Framingham Heart Study 3 rd generation participants with data on remote BP (2002–2005) and recent BP (2016–2019) who participated in 11 C-Pittsburgh Compound-B (PiB)-PET and/or 18 F-Flortaucipir (FTP)-PET scans between 2016 to 2022. Outcomes included global amyloid deposition (in the frontal, lateral temporal, parietal and retrosplenial cortices, FLR region) and entorhinal tau deposition. Results In 410 participants (mean age 40 ± 8 years at remote exam, 56 ± 8 years recent exam), the mean time between the remote exam BP measurement and PET was 16 ± 2 years. A steep change (slope of ≥0.5 or ≤−0.5 mmHg/year) in DBP over early to mid-life was associated with increased entorhinal tau-PET deposition (β = 0.02; 95% CI = 0.01, 0.04; p = 0.047), driven by a steep decline in DBP (β = 0.04; 95% CI = 0.01, 0.07; p = 0.01). Persistent hypertension, new-onset hypertension, resolved hypertension or a steep change in SBP were not associated with amyloid or tau burden. Conclusions In adults without clinical dementia, a steep DBP decline from early mid-life into mid-life was associated with tau deposition in the entorhinal cortex, one of the earliest affected regions in Alzheimer's disease. Maintaining normotension across the ∼15–16 years mid-life period may reduce the future risk of tau-PET burden in the brain.